Stimulant abuse and dependence are significant problems facing young adults in the United States. Around 20% of young adults report the use of illicit drugs between the ages of 18-20 years, and approximately one in seven subjects initiating stimulant use progress eventually to dependence. There is strong evidence that drug use and dependence are associated with deficits in inhibitory control. However, the basic cognitive and neural processes underlying such disinhibitory psychopathology are poorly understood. The long-term goal of this project is to delineate the neural provenance and behavioral consequence of inhibitory dysregulation in casual stimulant users, which would be valuable for developing novel tools for the identification of at-risk individuals, for preventative intervention, and for behavioral and pharmacological remediation. The specific aims are (1) to investigate the cognitive differences between stimulant users and normal controls, specifically evaluating the hypotheses that altered error processing and/or temporal perception in stimulant users contribute to impaired inhibitory control, (2) to identify the differential contributions of various brain regions in stopping behavior, as well as neurophysiological differences between stimulant users and matched controls, and (3) to uncover early behavioral and neurophysiological markers that predict whether a casual stimulant user will eventually develop dependent use or not. To achieve Aim 1, a novel, quantitative model for inhibitory control, differentiating the contributions of various cognitive processes such as sensory discrimination, temporal perception, reward/error processing, learning and adaptation, will be used to analyze stimulant users and matched controls performing the stop signal paradigm. To achieve Aim 2, subject- and trial-specific parametric regressors, corresponding to distinct cognitive processes of the quantitative model of Aim 1, will be used to identify the neural substrate (using fMRI data) of the various cognitive processes, and to characterize any neurophysiological differences between stimulant users and matches controls. To achieve Aim 3, three-year follow-up surveys, indicating which casual users eventually develop dependence, will be correlated with behavioral and neurophysiological measures collected in the original fMRI/behavioral experiments, to identify early behavioral and neurophysiological markers that predict transition from casual use to dependence. The behavioral and fMRI data have already been collected under a different grant;the follow-up survey, funded by another grant, will soon be completed. PUBLIC HEALTH RELEVANCE: Stimulant abuse and dependence are significant problems among young adults, making it imperative to identify the causative factors for stimulant use, as well as the nature of cognitive deficits in problem use, in order to develop more powerful diagnostic, preventative, and remedial procedures. In this project, a sophisticated, novel, quantitative model of inhibitory control will be developed, yielding a rich set of cognitive and behavioral measures that can characterizes subtle differences between stimulant users and control populations at different stages of drug use and addiction. The model will be applied to a large set of behavioral and functional MRI data of casual stimulant users and matched control subjects, with the goal of identifying behavioral and neural features that best predict whether an individual eventually develops addiction or not.